4-Methylbenzylidenecamphor (4-MBC; 5-400 μM; 48 hours) suppresses the growth of HTR8/SVneo cells [1]. Human trophoblast cell proliferation is induced by 4-methylbenzylidene camphor (10–50 μM; 48 hours) and results in an increase in the percentage of cells in the SubG1 phase [1]. 4-In 48 hours, 50 μM methylbenzylidenecamphor decreases human trophoblast cells' nutrition [1]. In human trophoblast cells, camphor (50 μM; 5-120 minutes) stimulates the signal amplifiers for PI3K/AKT and ERK1/2 [1]. 4-Methylbenzylidene camphor at 20–50 μM for 24 hours dramatically raises GPR56 and SEMA6 A.

Changes in gene expression and South African growth enhancement in newborns are caused by 4-Methylbenzylidenecamphor (4-MBC; 0.7, 7, 24, 47 mg/kg/day; given to parents in diet prior to mating, during pregnancy, and during fetal formulation) [2].

cell proliferation assay [1]
Cell Types: HTR8/SVneo Cell
Tested Concentrations: 0, 5, 10, 20, 50, 100 , 200 and 400 μM
Incubation Duration: 48 h
Experimental Results: Dose-dependently inhibited cell proliferation of HTR8/SVneo cell.

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Apoptosis analysis [1]
Cell Types: HTR8/SVneo Cell
Tested Concentrations: 10, 20, 50 μM
Incubation Duration: 48 h
Experimental Results: Early and late apoptotic cells increased Dramatically at 20 μM and 50 μM.

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Cell cycle analysis [1]
Cell Types: HTR8/SVneo Cell
Tested Concentrations: 5, 10, 20, 50 μM
Incubation Duration: 48 h
Experimental Results: The proportion of cells in the SubG1 phase gradually increased. Cell Invasion Analysis[1]
Cell Types: HTR8/SVneo Cell
Tested Concentrations: 50 μM
Incubation Duration: 48 hrs (hours)
Experimental Results: Invasiveness was Dramatically diminished by 81.5% Western Blot Analysis[1]
Cell Types: HTR8/SVneo Cell
Tested Concentrations: 50 μM
Incubation Duration: 0, 5, 15, 30, 60, 120 minutes
Experimental Results: The phosphorylation of AKT and its downstream kinase protein P70S6K peaked at 5 and 15 minutes respectively, then diminished after 30 minutes, an

Absorption, Distribution and Excretion
The maximum plasma concentration of enzacamene was 16ng/mL in healthy female volunteers following daily whole-body topical application of 2mg/cm^2 of sunscreen formulation at 10% (weight/weight) for four days. Blood concentration of enzacamene (4-MBC) and its main metabolite, 3-(4-carboxybenzylidene)camphor, peaked within 10 h after oral administration of enzacamene.
The urine concentration of 4 ng/mL and 4 ng/mL of enzacamene were observed in female and male volunteers, respectively. In a rat pharmacokinetic study, most of orally administered enzacamene was recovered in in feces as 3-(4-carboxybenzylidene)camphor and, to a smaller extent, as 3-(4-carboxybenzylidene)-6-hydroxycamphor. Glucuronides of both metabolites were also detectable in faces. In urine, one isomer of 3-(4-carboxybenzylidene)hydroxycamphor was the predominant metabolite [3-(4-carboxybenzylidene)-6-hydroxycamphor], the other isomers and 3-(4-carboxybenzylidene)camphor were only minor metabolites excreted with urine. Enterohepatic circulation of glucuronides derived from the two major 4-MBC metabolites may explain the slow excretion of 4-MBC metabolites with urine and the small percentage of the administered doses recovered in urine.
No pharmacokinetic data available.
No pharmacokinetic data available.

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Metabolism / Metabolites
Based on the findings of a rat pharmacokinetic study, it is proposed that absorbed enzacamene following oral administration undergo extensive first-pass hepatic metabolism. Following oral administration of enzacamene (4-MBC) in rats, detected metabolites in the plasma and urine were 3-(4-carboxybenzylidene)camphor and as four isomers of 3-(4-carboxybenzylidene)hydroxycamphor containing the hydroxyl group located in the camphor ring system with 3-(4-carboxybenzylidene)-6-hydroxycamphor as the major metabolite. However the blood concentrations of 3-(4-carboxybenzylidene)-6-hydroxycamphor were below the limit of detection following peak concentration. Via hydroxylation mediated by cytochrome P450 system, 3-(4-hydroxymethylbenzylidene)camphor is formed. This metabolite is further oxidized to 3-(4-carboxybenzylidene)camphor via oxidation of alcohol dehydrogenase and aldehyde dehydrogenase, and may be further hydroxylated to form 3-(4-carboxybenzylidene)-6-hydroxycamphor mediated by CYP450 system.

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Biological Half-Life
The half life of enzacamene (4-MBC) and its main metabolite, 3-(4-carboxybenzylidene)camphor, displayed half-lives of approximately 15 h after reaching peak plasma concentrations after oral administration in rats.

Protein Binding
No pharmacokinetic data available.

[1]. 4-Methylbenzylidene-camphor inhibits proliferation and induces reactive oxygen species-mediated apoptosis of human trophoblast cells. Reprod Toxicol. 2019 Mar:84:49-58.

[2]. Developmental toxicity of UV filters and environmental exposure: a review. Int J Androl. 2008 Apr;31(2):144-51.

Enzacamene is a monoterpenoid.
Commonly known as 4-methylbenzylidene-camphor (4-MBC), enzacamene is a camphor derivative and an organic chemical UV-B filter. It is used in cosmetic products such as sunscreen to provide skin protection against UV rays. While its effects on the human reproductive system as an endocrine disruptor are being investigated, its use in over-the-counter and cosmetic products is approved by Health Canada. Its tradenames include Eusolex 6300 (Merck) and Parsol 5000 (DSM).

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Drug Indication
Indicated for use as an active sunscreen agent.

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Mechanism of Action
Enzacamene absorbs UV-B rays. It is proposed that enzacamene exerts estrogen-like activities in the same direction as endogenous estrogens via nonclassical estrogen signaling mechanisms that do not involve gene regulation by the nuclear ER. It binds to cytosolic estradiol binding sites of estrogen receptors with low to moderate affinity compared to that of the endogenous agonist. Based on the findings of a study with _Xenopus_ hepatocytes in culture, enzacamene has a potential to induce the ER gene only at higher concentrations (10–100 μmol/L). While enzacamene was not shown to activate estrogen-dependent gene transcription when tested in an ER reporter gene assay in yeast cells, it was demonstrated in _Xenopus_ hepatocytes cultures that activate ER-dependent signaling mechanisms leading to altered gene expression. In micromolar concentrations, enzacamene accelerates cell proliferation rate in MCF-7 human breast cancer cells.

C18H22O

254.3667

254.167

36861-47-9

4-Methylbenzylidene camphor-d4;1219806-41-3

6434217

White to off-white solid powder

1.1±0.1 g/cm3

371.9±22.0 °C at 760 mmHg

66-68°C

168.9±13.2 °C

0.0±0.8 mmHg at 25°C

1.583

4.95

0

1

1

19

423

0

CC1=CC=C(C=C1)/C=C/2\C3CCC(C2=O)(C3(C)C)C

HEOCBCNFKCOKBX-SDNWHVSQSA-N

InChI=1S/C18H22O/c1-12-5-7-13(8-6-12)11-14-15-9-10-18(4,16(14)19)17(15,2)3/h5-8,11,15H,9-10H2,1-4H3/b14-11+

(3E)-1,7,7-trimethyl-3-[(4-methylphenyl)methylidene]bicyclo[2.2.1]heptan-2-one

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~100 mg/mL (~393.13 mM)
H2O : < 0.1 mg/mL

Solubility in Formulation 1: 2.5 mg/mL (9.83 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: 2.5 mg/mL (9.83 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (9.83 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)